Human platelets synthesize prostaglandins during blood clotting and platelet aggregation. The precursor of these prostaglandins, arachidonic acid, induces platelet aggregation in vitro and in vivo in association with prostaglandin synthesis. The purpose of this work is to investigate further the synthesis of prostaglandin by platelets and elucidate its relevance to hemostasis and inflammation. We propose to determine the kinds and amounts of prostaglandins produced by platelets from normal human adults, and to investigate the effects of prostaglandin metabolites and novel prostaglandins on the functions of platelets from normal humans. We will thoroughly investigate the agents that trigger, modify and inhibit the production of platelet prostaglandins. Experiments will be done to determine the cause of sudden death in rabbits after an injection of arachidonic acid into the ear vein. This study includes the characterization of the phospholipase A and the prostaglandin synthetase enzyme systems of human platelets. Special attention will be paid to the effects of anti-inflammatory agents such as aspirin, indomethacin and other drugs which inhibit prostaglandin formation to see whether there is a general relationship between inhibition of prostaglandin synthesis and inhibition of platelet aggregation. Finally, we shall search for abnormal prostaglandin synthesis by the platelets of selected patients. The methods employed include tests of platelet aggregation, the release reaction, determinations of phospholipase A, transmission electron microscopy and scanning electron microscopy of platelet thrombi and blood vessels, and qualitative and quantitative determinations of prostaglandins by thin layer chromatography, bioassay and radioimmunoassay.